Cited by 324Mitochondrial Function and PathologyMetabolism and Genetic DisordersGenomics and Rare Diseases

Progressive Increase of the Mutated Mitochondrial DNA Fraction in Kearns-Sayre Syndrome

Larsson, Nils-göran, Holme, Elisabeth, Kristiansson, Bengt, Oldfors, Anders, Tulinius, Mår·1990·Pediatric Research

Abstract

We have performed morphologic and biochemical studies in three pediatric cases of Kearns-Sayre syndrome. All cases had heteroplasmy with a high percentage of mitochondrial DNA (mtDNA) with deletion in muscle. The deletions were mapped to the same region of mtDNA but were of different sizes. The same type of deletion could also be detected in fibroblasts from all cases but the percentage was considerably lower. In two cases, an increase with time of the mutated mtDNA fraction in muscle was found and this increase paralleled the progression of the disease. Oximetric evaluation of respiratory-chain function in isolated muscle mitochondria showed a complex I deficiency in one case and was normal in the two other cases. Comparison of the fractional concentration of mtDNA with deletion in muscle and isolated mitochondria showed that the isolated mitochondria were not representative of the mitochondrial population in muscle. Mitochondria with high percentage of mtDNA with deletion were selectively lost. The finding of different mitochondrial populations is in good agreement with the morphology. One case spontaneously recovered from an infantile sideroblastic anemia before the development of Kearns-Sayre syndrome. The anemia was of the same type as that in Pearson's syndrome, a mitochondrial disorder with high amounts of mtDNA with deletion in blood cells. These findings indicate that the phenotype of a mtDNA deletion disorder can change with time and is governed by the fractional co…

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Crossref · 10.1203/00006450-199008000-00011

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  • The tissue-specific knockout animals reproduce important pathophysiological features found in human patients with mitochondrial myopathy, i.e., RRFs with COX deficiency, accumulation of abnormally appearing mitochondria, and progressively deteriorating respiratory chain function in skeletal muscle.

    “These tissue-specific knockout animals reproduce important pathophysiological features found in human patients with mitochondrial myopathy, i.e., RRFs with COX deficiency (1), accumulation of abnormally appearing mitochondria (23), and progressively deteriorating respiratory chain function in skeletal muscle (24,25).”

    From Increased mitochondrial mass in mitochondrial myopathy mice (2002) · cites this paper as [24]

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Authors
Larsson, N.-G., Holme, E., Kristiansson, B., Oldfors, A., & Tulinius, M.
Affiliations
Sahlgrenska University Hospital (SE)
Venue
Pediatric Research
Published
1990-08
Volume
28
Issue
2
Pages
131-136
ISSN
  • 0031-3998 (ISSN-L)
  • 1530-0447
OpenAlex
W2022312470
Cited by
324
References
6
Citations by year
2026: 3 · 2025: 8 · 2024: 9 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 8 · 2019: 4 · 2018: 6 · 2017: 6 · 2016: 2 · 2015: 3 · 2014: 10 · 2013: 7 · 2012: 4
FWCI
6.56
Type
journal article
Language
en
Open access
closed
Locations
  • Pediatric Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Bernadotte Foundation For Children’s Eyecare
  • Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Keywords
Kearns-Sayre syndrome, mitochondrial DNA deletions, heteroplasmy, muscle mitochondria, disease progression, Pearson syndrome, fibroblasts
MeSH terms
Adolescent, Adult, Bone Marrow, Chromosome Deletion, Chromosome Mapping, DNA, Mitochondrial, Female, Humans, Kearns-Sayre Syndrome, Male, Mitochondria, Muscle, Mutation, Ophthalmoplegia, Time Factors

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